NCT05056727

Brief Summary

The purpose of this study is to evaluate the effect of Sodium Zirconium Cyclosilicate (SZC), as adjunct to ACEi/ARB therapy (lisinopril or valsartan), on slowing CKD progression (assessed as the reduction in participant's glomerular filtration rate \[eGFR\] decline over time) in participants with hyperkalaemia or at high risk of hyperkalaemia.

Trial Health

68
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
1,112

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Sep 2021

Geographic Reach
21 countries

276 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 1, 2021

Completed
23 days until next milestone

First Posted

Study publicly available on registry

September 24, 2021

Completed
6 days until next milestone

Study Start

First participant enrolled

September 30, 2021

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 7, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 7, 2024

Completed
1.9 years until next milestone

Results Posted

Study results publicly available

January 8, 2026

Completed
Last Updated

January 8, 2026

Status Verified

December 1, 2025

Enrollment Period

2.4 years

First QC Date

September 1, 2021

Results QC Date

February 12, 2025

Last Update Submit

December 17, 2025

Conditions

Keywords

Renal Insufficiency, ChronicChronic Kidney DiseasesHyperkalemia

Outcome Measures

Primary Outcomes (2)

  • Total eGFR Slope (Coprimary Analysis #1)

    Total eGFR slope, Baseline (Maintenance phase) to visit 17 (week 69)

    Baseline (Maintenance phase) to visit 17 (week 69)

  • Chronic eGFR Slope (Coprimary Analysis #2)

    Chronic eGFR slope, 12 weeks to visit 17 (week 69)

    12 weeks to visit 17 (week 69)

Secondary Outcomes (3)

  • Incidence of the Composite of Kidney Failure Outcomes

    From Baseline (Maintenance phase) up to week 97 (Maintenance phase)

  • Incidence of RAASi Reduction

    From Baseline (Maintenance phase) up to week 97 (Maintenance phase)

  • UACR

    At visit 13 (week 24)

Study Arms (2)

Sodium Zirconium Cyclosilicate (SZC)

EXPERIMENTAL

SZC 5 g every other day to 15 g once daily + Lisinopril/Valsartan

Drug: Sodium Zirconium Cyclosilicate (SZC)Drug: LisinoprilDrug: ValsartanDrug: Irbesartan

Placebo

PLACEBO COMPARATOR

Placebo + Lisinopril/Valsartan

Drug: PlaceboDrug: LisinoprilDrug: ValsartanDrug: Irbesartan

Interventions

Powder for oral suspension in a sachet. Placebo to match 5 or 10 g. Single dose will consist of 1-3 sachets. During Maintenance Phase: \- Single dose contains 5 g placebo administered every other day or 5, 10, or 15 g placebo administered once daily that should be suspended in 45 mL of water.

Placebo

Tablet for oral administration. Unit dose strength: 2.5, 5, 10 or 20 mg. Dosage level: 5, 10, 20, or 40 mg administered once daily.

PlaceboSodium Zirconium Cyclosilicate (SZC)

Tablet or capsule for oral administration. Unit dose strength: 40, 80 or 160 mg. Dosage level: 40, 80, 160, or 320 mg administered once daily.

PlaceboSodium Zirconium Cyclosilicate (SZC)

Tablet for oral administration. Unit dose strength: 75, 150 or 300 mg. Dosage level: 75, 150, or 300 mg administered once daily. The study is designed to use valsartan as the selected ARB therapy adjunct to SZC. However, if an actual shortage of valsartan in a local market jeopardises the ability of participants to enter or continue in the study, valsartan can be temporarily substituted with irbesartan until the shortage of valsartan is resolved.

PlaceboSodium Zirconium Cyclosilicate (SZC)

Powder for oral suspension in a sachet. Unit dose strength: 5 or 10 g SZC. Single dose will consist of 1-3 sachets. During Initiation Phase: * S-K \> 5 to ≤ 6.5 mmol/L (measured by L-Lab): Single dose contains 10 g SZC that should be suspended in 45 mL of water. The 10 g SZC single dose should be administered three times daily for up to 72 hours until normokalaemic (S-K 3.5-5.0 mmol/L); the total daily dose is 30 g SZC. * S-K ≥ 3.5 to ≤ 5 mmol/L (measured by L-Lab): Single dose contains 5 g SZC that should be suspended in 45 mL of water and administered once daily for 48 hours. During Run-in and Maintenance Phases: \- Single dose contains 5 g SZC administered every other day or 5, 10, or 15 g SZC administered once daily that should be suspended in 45 mL of water.

Also known as: Lokelma TM
Sodium Zirconium Cyclosilicate (SZC)

Eligibility Criteria

Age18 Years - 130 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and protocol
  • Must be ≥ 18 years of age at the time of signing the informed consent.
  • Must have eGFR ≥ 25 and ≤ 59 mL/min/1.73m2 as calculated by central laboratory (CKD-EPI formula) at screening (Visit 1)
  • Must have UACR ≥ 200 and ≤ 5000 mg/g as calculated by central laboratory at screening (Visit 1). If the first sample does not fulfil eligibility criteria, a second sample can be obtained during the screening period; if so, the UACR measurement from the second sample must be within the eligibility range.
  • Any of the following criteria, a or b, at screening (Visit 1):
  • Cohort A: Hyperkalaemia (S-K \> 5.0 to ≤ 6.5 mmol/L) as measured by the central laboratory, and on adequate\* or limited\*\* RAASi therapy due to hyperkalaemia.
  • Cohort B: Normokalaemia (S-K ≥ 3.5 to ≤ 5.0 mmol/L) as measured by the central laboratory and on limited\*\* RAASi therapy due to high risk of hyperkalaemia. High risk of hyperkalaemia is defined as:
  • (i) Participants with a previous medical history or record of hyperkalaemia within the prior 24 months, who are on limited\*\* RAASi therapy despite indication in CKD.
  • (ii) Participants in whom RAASi therapy is indicated in CKD, who are on limited\*\* RAASi therapy and have S-K ≥ 4.7 to ≤ 5.0 mmol/L.
  • (iii) Participants in whom RAASi therapy has been discontinued or reduced to suboptimal\* doses because of hyperkalaemia.
  • \*Adequate RAASi dose levels are defined in protocol; doses lower than these are considered as suboptimal.
  • \*\*Limited RAASi therapy is defined as no or suboptimal RAASi therapy according to dosing guidance provided in protocol.
  • If on thiazide or loop diuretics, the dose must have been stable for 2 weeks prior to screening (Visit 1).
  • If on RAASi therapy, the dose must have been stable for one month prior to screening (Visit 1) and remain stable during screening.
  • If on an SGLT2i treatment (ie, dapagliflozin and canagliflozin), finerenone, or any other medications in these 2 classes that are approved for CKD, the dose must have been stable for 3 months prior to screening (Visit 1).
  • +1 more criteria

You may not qualify if:

  • New York Heart Association class III to IV congestive heart failure at the time of screening (Visit 1) or previous history of severe or symptomatic heart failure.
  • Myocardial infarction, unstable angina, stroke, or transient ischaemic attack within 3 months prior to screening (Visit 1).
  • Participants with a known history of systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg within 2 weeks prior to screening (Visit 1) are excluded. In addition, any participant with systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg as measured at screening (Visit 1) and confirmed by repeated measurement is excluded. Participants may be rescreened once blood pressure is controlled.
  • QTcF \> 550 msec at screening (Visit 1).
  • History of QT prolongation associated with other medications that required discontinuation of that medication.
  • Congenital long QT syndrome.
  • Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation and heart rate controlled by medication are permitted.
  • Lupus nephritis or anti-neutrophil cytoplasmic antibody-associated vasculitis.
  • Change in renal function requiring hospitalisation or dialysis within 3 months prior to screening (Visit 1).
  • History of renal transplant (or anticipated need for renal transplant during the study).
  • Severe hepatic impairment, biliary cirrhosis, or cholestasis.
  • History of hereditary or idiopathic angioedema.
  • Any prior hypersensitivity to ACEi or ARB that in the investigator's judgment precludes use of lisinopril and valsartan/irbesartan. Prior hypersensitivity reactions to consider include, but are not limited to, development of angioedema, icterus, hepatitis, or neutropaenia or thrombocytopaenia requiring treatment modification.
  • Known hypersensitivity or previous anaphylaxis to SZC or to components thereof.
  • Any condition outside the CV and renal disease area such as, but not limited to, malignancy, with a life expectancy of less than 2 years based on investigator´s clinical judgment.
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (276)

Research Site

Surprise, Arizona, 85374, United States

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Tucson, Arizona, 85741, United States

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Canyon Country, California, 91351, United States

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Chula Vista, California, 91910, United States

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Northridge, California, 91324, United States

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San Dimas, California, 91773, United States

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South Gate, California, 90280, United States

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Tarzana, California, 91356, United States

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Denver, Colorado, 80230, United States

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Boynton Beach, Florida, 33435, United States

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Hialeah, Florida, 33012, United States

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Lauderdale Lakes, Florida, 33313, United States

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Ocoee, Florida, 34761, United States

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Temple Terrace, Florida, 33637, United States

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Nampa, Idaho, 83687, United States

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Chicago, Illinois, 60643, United States

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Oak Brook, Illinois, 60523, United States

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Fort Wayne, Indiana, 46804, United States

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Louisville, Kentucky, 40205, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02115, United States

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Flint, Michigan, 48532, United States

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Saint Clair Shores, Michigan, 48081, United States

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Columbia, Missouri, 65201, United States

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Kansas City, Missouri, 64111, United States

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Albuquerque, New Mexico, 87109, United States

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Albany, New York, 12205, United States

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Great Neck, New York, 11021, United States

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Winston-Salem, North Carolina, 27103, United States

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Cincinnati, Ohio, 45267, United States

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Bethlehem, Pennsylvania, 18017, United States

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Chester, Pennsylvania, 19013, United States

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Columbia, South Carolina, 29203, United States

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Orangeburg, South Carolina, 29118, United States

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Chattanooga, Tennessee, 37404, United States

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Arlington, Texas, 76015, United States

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Fort Worth, Texas, 76164, United States

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Houston, Texas, 77004, United States

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Houston, Texas, 77054, United States

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Houston, Texas, 77099, United States

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San Antonio, Texas, 78212, United States

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Newport News, Virginia, 23606, United States

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Buenos Aires, ARG 1425, Argentina

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Buenos Aires, C1429BWN, Argentina

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CABA, C1440AAD, Argentina

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La Plata, 1900, Argentina

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Mar del Plata, 7600, Argentina

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Mar del Plata, B7600, Argentina

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Rosario, 2000, Argentina

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San Vicente, 5006, Argentina

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Sarandí, B1872EEC, Argentina

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Curitiba, 80440-020, Brazil

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Fortaleza, 60115282, Brazil

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Joinville, 89227-680, Brazil

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Maringá, 87060-040, Brazil

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Porto Alegre, 90020-090, Brazil

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Porto Alegre, 90160-093, Brazil

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São Paulo, 04039-000, Brazil

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São Paulo, 05403-9000, Brazil

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Blagoevgrad, 2700, Bulgaria

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Botevgrad, 2140, Bulgaria

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Dupnitsa, 2600, Bulgaria

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Gorna Oryahovitsa, 5100, Bulgaria

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Gotse Delchev, 2900, Bulgaria

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Kozloduy, 3320, Bulgaria

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Lom, 3600, Bulgaria

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Pleven, 5800, Bulgaria

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Plovdiv, 4000, Bulgaria

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Plovdiv, 4001, Bulgaria

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Plovdiv, 4004, Bulgaria

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Samokov, 2000, Bulgaria

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Sandanski, 2800, Bulgaria

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Silistra, 7500, Bulgaria

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Sliven, 8800, Bulgaria

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Smolyan, 3700, Bulgaria

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Stara Zagora, 6000, Bulgaria

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Yambol, 8600, Bulgaria

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Saint John, New Brunswick, E2L 4L2, Canada

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Oshawa, Ontario, L1G 2B9, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Montreal, Quebec, H4J 1C5, Canada

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Baotou, 014010, China

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Beijing, 100029, China

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Beijing, 100034, China

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Beijing, 100044, China

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Beijing, 100191, China

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Beijing, 102206, China

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Beijing, 102218, China

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Changchun, 130041, China

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Changsha, 410013, China

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Chengdu, 610041, China

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Chengdu, 610072, China

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Chongqing, 400010, China

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Guangzhou, 510000, China

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Guangzhou, 510062, China

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Guangzhou, 510180, China

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Guangzhou, 510630, China

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Guiyang, 550002, China

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Hangzhou, 310014, China

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Hefei, 230601, China

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Hengyang, 421001, China

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Huizhou, 516001, China

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Lanzhou, 730030, China

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Nanchang, 330006, China

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Nanjing, 210009, China

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Nanjing, 210011, China

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Nanjing, 210029, China

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Ningbo, 315010, China

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Sanya, 572000, China

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Shanghai, 200025, China

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Shanghai, 200040, China

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Shanghai, 201199, China

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Shanghai, 201210, China

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Shantou, 515041, China

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Shengyang, 110004, China

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Shenyang, 110001, China

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Shenzhen, 518036, China

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Taiyuan, 030012, China

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Ürümqi, 830054, China

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Wuhan, 430010, China

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Wuhan, 430060, China

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Wuxi, 214023, China

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Xi'an, 710061, China

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Xuzhou, 221000, China

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Yantai, 264000, China

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Yinchuan, 750004, China

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Zhengzhou, 450052, China

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Zhuzhou, 412007, China

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Coimbatore, 641018, India

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Kolkata, 700020, India

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Madurai, 625107, India

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New Delhi, 110029, India

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Bari, 70124, Italy

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Bassano del Grappa, 36061, Italy

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Bologna, 40138, Italy

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Brescia, 25123, Italy

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Messina, 98125, Italy

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Pavia, 27100, Italy

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Roma, 00161, Italy

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Roma, 00168, Italy

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Rozzano, 20089, Italy

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San Giovanni Rotondo, 71013, Italy

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Verona, 37126, Italy

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Amagasaki-shi, 660-8550, Japan

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Atsugi-shi, 243-0035, Japan

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Chiba, 260-8712, Japan

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Chuo-shi, 409-3898, Japan

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Chūōku, 103-0002, Japan

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Chūōku, 104-8560, Japan

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Fukuoka, 814-0180, Japan

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Kamakura-shi, 247-0056, Japan

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Kanoya-shi, 893-0015, Japan

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Kasugai-shi, 486-8510, Japan

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Kawachinagano-shi, 586-8521, Japan

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Kawasaki-shi, 211-8510, Japan

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Kitakyushu, 805-8508, Japan

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Kitakyushu-shi, 802-8555, Japan

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Koriyama-shi, 963-8052, Japan

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Koshigaya-shi, 343-8555, Japan

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Kumamoto, 861-8520, Japan

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Kure-shi, 737-0023, Japan

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Marugame-shi, 763-8502, Japan

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Matsumoto-shi, 390-8621, Japan

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Matsusaka-shi, 515-8557, Japan

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Matsuyama, 790-8524, Japan

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Nagoya, 457-8511, Japan

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Nagoya, 466-8650, Japan

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Naka, 311-0113, Japan

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Noda, 278-8501, Japan

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Osaka, 543-8922, Japan

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Osaka, 559-0012, Japan

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Ōita, 870-0033, Japan

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Ōmihachiman, 523-0082, Japan

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Sakaishi, 593-8304, Japan

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Takarazuka-shi, 665-0873, Japan

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Toyota, 470-0396, Japan

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Toyota-Shi, 471-8513, Japan

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Tsu, 514-8507, Japan

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Tsuchiura-shi, 300-0028, Japan

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Urayasu-shi, 279-0021, Japan

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Yaizu-shi, 425-8505, Japan

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Yokohama, 227-8501, Japan

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Yokohama, 234-0054, Japan

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Yokohama, 236-0004, Japan

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Yonago-shi, 683-8605, Japan

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Alor Star, 5460, Malaysia

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Batu Caves, 68100, Malaysia

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Johor Bahru, 80100, Malaysia

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Kajang, 43000, Malaysia

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Kuala Lumpur, 50586, Malaysia

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Kuala Lumpur, 56000, Malaysia

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Kuala Lumpur, 59100, Malaysia

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Seri Manjung, 32040, Malaysia

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Cuauhtémoc, 06700, Mexico

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Culiacán, 80230, Mexico

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Guadalajara, 44670, Mexico

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Mazatlán, 82000, Mexico

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Mérida, 97070, Mexico

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Mérida, 97130, Mexico

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México, 03100, Mexico

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México, 06700, Mexico

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San Luis Potosí City, 78250, Mexico

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Veracruz, 91900, Mexico

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Davao City, PH-8000, Philippines

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Iloilo City, 5000, Philippines

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Krakow, 31-156, Poland

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Lodz, 92-213, Poland

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Poznan, 61-485, Poland

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Rzeszów, 35-055, Poland

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Tczew, 83-110, Poland

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Ponce, 00717, Puerto Rico

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Aramil, 624002, Russia

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Moscow, 123182, Russia

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Perm, 614000, Russia

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Rostov-on-Don, 344022, Russia

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Saint Petersburg, 191167, Russia

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Almería, 4009, Spain

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Barcelona, 8003, Spain

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Getafe, 28905, Spain

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L'Hospitalet de Llobregat, 08907, Spain

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Lugo, 27004, Spain

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Madrid, 28040, Spain

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Santa Cruz de Tenerife, 38010, Spain

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Seville, 41009, Spain

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Valencia, 46010, Spain

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Valencia, 46014, Spain

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Hualien City, 97002, Taiwan

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Kaohsiung City, 81362, Taiwan

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Kaohsiung City, 82445, Taiwan

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Kaohsiung City, 833, Taiwan

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Keelung, 20448, Taiwan

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New Taipei City, 220216, Taiwan

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New Taipei City, 23561, Taiwan

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Taichung, 40201, Taiwan

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Taichung, 40705, Taiwan

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Tainan, 70403, Taiwan

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Tainan, 710, Taiwan

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Taipei, 10002, Taiwan

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Taipei, 110, Taiwan

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Taipei, 114, Taiwan

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Taoyuan District, 333, Taiwan

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Bangkok, 10330, Thailand

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Bangkok, 10700, Thailand

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Chaingmai, 50200, Thailand

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Hat Yai, 90110, Thailand

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Ratchathewi, 10400, Thailand

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Adapazarı, 54100, Turkey (Türkiye)

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Ankara, 06230, Turkey (Türkiye)

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Ankara, 06340, Turkey (Türkiye)

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Ankara, 6230, Turkey (Türkiye)

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Antalya, 07059, Turkey (Türkiye)

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Gaziantep, 27310, Turkey (Türkiye)

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Istanbul, Turkey (Türkiye)

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Izmir, 35040, Turkey (Türkiye)

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Kahramanmaraş, 46100, Turkey (Türkiye)

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Kayseri, 38039, Turkey (Türkiye)

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Kocaeli, 41380, Turkey (Türkiye)

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Dnipropetrovsk, 49005, Ukraine

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Kharkiv, 61039, Ukraine

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Kyiv, 02125, Ukraine

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Kyiv, 03057, Ukraine

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Kyiv, 04050, Ukraine

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Kyiv, 04053, Ukraine

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Lutsk, 43005, Ukraine

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Vinnytsia, 21028, Ukraine

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Zaporizhzhia, 69001, Ukraine

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Zhytomyr, 10002, Ukraine

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Biên Hòa, 810000, Vietnam

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Da Nang, 55000, Vietnam

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Hanoi, 100000, Vietnam

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Ho Chi Minh City, 10000, Vietnam

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Ho Chi Minh City, 700000, Vietnam

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Ho Chi Minh City, 70000, Vietnam

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Huế, 530000, Vietnam

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Related Links

MeSH Terms

Conditions

Renal Insufficiency, ChronicHyperkalemia

Interventions

sodium zirconium cyclosilicateLisinoprilValsartanIrbesartan

Condition Hierarchy (Ancestors)

Renal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsWater-Electrolyte ImbalanceMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

DipeptidesOligopeptidesPeptidesAmino Acids, Peptides, and ProteinsTetrazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsValineAmino Acids, Branched-ChainAmino AcidsAmino Acids, EssentialBiphenyl CompoundsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsSpiro CompoundsPolycyclic Compounds

Limitations and Caveats

The study was terminated early due to recruitment challenges (not safety concerns). The ensuing small number of fully evaluable subjects (716 randomized vs planned 1360) and short follow up (mean 8 - 9 months vs planned 24 months) had a heavy negative impact on the formal statistical analyses, especially slope analyses, and therefore preclude any meaningful conclusions on eGFR slopes.

Results Point of Contact

Title
Global Clinical Lead
Organization
AstraZeneca

Study Officials

  • Glenn M. Chertow, MD, MPH

    Stanford University School of Medicine, Stanford, CA USA

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 1, 2021

First Posted

September 24, 2021

Study Start

September 30, 2021

Primary Completion

February 7, 2024

Study Completion

February 7, 2024

Last Updated

January 8, 2026

Results First Posted

January 8, 2026

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will share

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
More information

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